intracoronary infusion of bm-mnc early or late after ami

Intracoronary  infusion  of  BM-­‐MNC  early  or  late  a5er  AMI  -­‐  

4  months  results  of  the  SWISS-­‐AMI  trial  

Daniel Sürder, MD Fondazione Cardiocentro Ticino Lugano – Switzerland daniel.suerder@cardiocentro.org

ClinicalTrials.gov Identifier: NCT00355186

2012  Scien?fic  Sessions  of  the  AHA  -­‐  Late  breaking  trials  

swissami

swissami

swissami

Background Intracoronary BM-MNC infusion in the infarct related artery after AMI has been shown to be safe; however, its efficacy is still debated.

swissami

swissami

swissami

Optimal timing for cell delivery post-AMI is unknown. Previous studies indicated potential time dependent efficacy in subgroup analyses.

?

Schächinger V, et al N Engl J Med 2006

Study  design  &  Methods   BM-MNC - BM-Aspiration from the

iliac crest (60ml) - Centralized cell

processing using density gradient centrifugation, without adding Heparin (UTC Lugano)

CMR - Standardized protocol

including cine and delayed enhancement

- Core-lab analysis (University Hospital Zurich)

swissami

swissami

swissami

EF  <45%  

within  24h  

Sürder et al. Am Heart J 2010

Endpoints  &  sample  size   Primary endpoint:   Change in global LVEF at 4 mo. vs. baseline

  Assumption: Δ LVEF = 3.5%; SD of 6-7%; drop out = 10%

  For a independent sample t-test 58 paired CMR per group

are needed - including drop out n = 64 per group

Secondary endpoints:   Change in LV volumes, infarct size (DE CMR) and regional

myocardial thickening

  MACE (death, MI, coronary revascularization, stroke)

  Predictors for efficacy (time to reperfusion, transmurality,

microvascular obstruction)

swissami

swissami

swissami

swissami

swissami

swissami

Pa?ent  flow  chart  

Total  345  CMR  analyses  (24.430  slices)  

swissami

swissami

swissami

*  control  vs.  early  ‡  control  vs.  late    

Baseline  characteris?cs  of  the  pa?ents  

swissami

swissami

swissami

*  control  vs.  early  ‡  control  vs.  late    

Characteris?cs  of  index  AMI  

swissami

swissami

swissami

*    n  =  29  **    n  =  30  

Characteris?cs  of  BM-­‐MNC  

swissami

swissami

swissami Results  

Mean  LVEF  at  baseline  and  4  months  

p  =  0.74                                            p  =  0.12                                        p  =  0.45  

!

Primary  Endpoint  

swissami

swissami

swissami

Mean  change  in  LVEF  4  months  vs.  baseline  

Primary  Endpoint  

swissami

swissami

swissami

Mean  change  in  LVEF  4  months  vs.  baseline  

Adjus?ng  for  baseline  LVEF  with  ANCOVA  tes?ng:  

Es$mate  (95%CI)          p-­‐value  

1.25  (-­‐1.83  to  4.32)          0.42      early  vs.  control  

0.55  (-­‐2.61  to  3.71)          0.73      late  vs.  control  

swissami

swissami

swissami

P  =  0.03  vs.  control  

P  =  0.89  vs.  control  

P  =  0.07  vs.  control  

P  =  0.79  vs.  control  

Secondary  Endpoints  

Control                            Early                                Late   Control                            Early                                Late  

100  

50  

0  

-­‐50  

-­‐100  

LVEDV  (ml)   LVESV  (ml)  

Change  in  LV-­‐volumes  4  months  vs.  baseline  

swissami

swissami

swissami

P  =  0.82  vs.  control  

P  =  0.59  vs.  control  

20  

0  

-­‐20  

-­‐40  

-­‐60  

Control                            Early                                Late   Control                            Early                                Late  

10  

5  

0  

-­‐5  

Secondary  Endpoints  

Change  in  scar  size  and  regional  LV  funcSon  

Scar  size  (g)   Myocardial  thickening  in    the  infarct  territory  (mm)  

P  =  0.54  vs.  control  

P  =  0.67  vs.  control  

swissami

swissami

swissami Predictors  for  treatment  efficacy  

!

Change    in  LVEF  

<  4.5h   <  4.5h  >  4.5h   >  4.5h  

swissami

swissami

swissami Clinical  events  during  follow  up  

*  control  vs.  early  ‡  control  vs.  late    

Summary  

Intracoronary  infusion  of  BM-­‐MNC,  either  5-­‐7  d  or  3-­‐4  wks  a\er  primary  PCI  for  STEMI,  did  not  improve  LV-­‐func?on  as  assessed  by  CMR  at  4  months  compared  with  control.  

Subgroup  analysis  indicates  potenSal  benefit  of  i.c.  BM-­‐MNC  in  paSents  with  early  reperfusion  (within  4.5  h  from  the  onset  of  pain).  

swissami

swissami

swissami

Summary  

Intracoronary  infusion  of  BM-­‐MNC,  either  5-­‐7  d  or  3-­‐4  wks  a\er  primary  PCI  for  STEMI,  did  not  improve  LV-­‐func?on  as  assessed  by  CMR  at  4  months  compared  with  control.  

Subgroup  analysis  indicates  potenSal  benefit  of  i.c.  BM-­‐MNC  in  paSents  with  early  reperfusion  (within  4.5  h  from  the  onset  of  pain).  

swissami

swissami

swissami

Adapted from Jeevanantham et al. Circulation 2012

SWISS  AMI:  Δ  LVEF  early  vs.  control  =  2.1%  

Acknowledgements  

swissami

swissami

swissamiPI:  Roberto  CorS  Co-­‐PI:  Daniel  Sürder  

CMR  core  lab:    Robert  Manka  Juerg  Schwiber  ValenSn  Gisler  Florian  Mayer  ChrisSna  Scheiben  

USZ:    Ines  Bühler  Simone  Kaufmann  

Inselspital:    Aris  MoschoviSs  Stephan  Windecker  Andreas  Wahl  Christa  Schönenberger  

KS  Luzern:  Paul  Erne    Michel  Zuber  Christof  Auf  der  Maur  Peiman  Jamshidi  Doris  Erne  Brigiba  Mehmann  

SebasSan  Stoll  Christoph  Wyss  Manuel  Zipponi  

CCT  /  UTC  core  lab:    Tiziano  Mocceh  Lucia  Turchebo  Sabrina  Soncin  Viviana  Lo  Cicero  Marina  Radrizzani  Giuseppe  Astori  Elena  Pecchi